Reduced expression of secretogranin VGF in laryngeal squamous cell carcinoma.

Laryngeal cancer accounts for one-third of all head and neck tumors, with squamous cell carcinoma (SCC) being the most predominant type, followed by neuroendocrine tumors. Chromogranins, are commonly used as biomarkers for neuroendocrine tumors, including laryngeal cancer. It has been reported that secretogranin VGF, a member of the chromogranin family, can be also used as a significant biomarker for neuroendocrine tumors.

What substance P might tell us about the prognosis and mechanism of Parkinson's disease?

The neuropeptide substance P (SP) plays an important role in neurodegenerative disorders, among which Parkinson's disease (PD). In the present work we have reviewed the involvement of SP and its preferred receptor (NK1-R) in motor and non-motor PD symptoms, in both PD animal models and patients. Despite PD is primarily a motor disorder, non-motor abnormalities, including olfactory deficits and gastrointestinal dysfunctions, can represent diagnostic PD predictors, according to the hypothesis that the olfactory and the enteric nervous system represent starting points of neurodegeneration, ascending to the brain via the sympathetic fibers and the vagus nerve.

Involvement of Bradykinin Receptor 2 in Nerve Growth Factor Neuroprotective Activity.

Neurotrophin nerve growth factor (NGF) has been demonstrated to upregulate the gene expression of bradykinin receptor 2 (B2R) on sensory neurons, thus facilitating nociceptive signals. The aim of the present study is to investigate the involvement of B2R in the NGF mechanism of action in nonsensory neurons in vitro by using rat mixed cortical primary cultures (CNs) and mouse hippocampal slices, and in vivo in Alzheimer's disease (AD) transgenic mice (5xFAD) chronically treated with NGF. A significant NGF-mediated upregulation of B2R was demonstrated by microarray, Western blot, and immunofluorescence analysis in CNs, indicating microglial cells as the target of this modulation.

TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling.

VGF gene encodes for a neuropeptide precursor of 68 kDa composed by 615 (human) and 617 (rat, mice) residues, expressed prevalently in the central nervous system (CNS), but also in the peripheral nervous system (PNS) and in various endocrine cells. This precursor undergoes proteolytic cleavage, generating a family of peptides different in length and biological activity. Among them, TLQP-21, a peptide of 21 amino acids, has been widely investigated for its relevant endocrine and extraendocrine activities.

Involvement of the Chemokine Prokineticin-2 (PROK2) in Alzheimer's Disease: From Animal Models to the Human Pathology.

Among mediators of inflammation, chemokines play a pivotal role in the neuroinflammatory process related to Alzheimer's disease (AD). The chemokine Bv8/prokineticin 2 (PROK2) is a critical player in inflammatory and neuroinflammatory diseases and has been demonstrated to be involved in Aβ toxicity. The aim of the present study was to extend the research to rats chronically intracerebroventricularly (i.

Neuropeptides in Alzheimer's Disease: An Update.

Neuropeptides are small proteins broadly expressed throughout the central nervous system, which act as neurotransmitters, neuromodulators and neuroregulators. Growing evidence has demonstrated the involvement of many neuropeptides in both neurophysiological functions and neuropathological conditions, among which is Alzheimer's disease (AD). The role exerted by neuropeptides in AD is endorsed by the evidence that they are mainly neuroprotective and widely distributed in brain areas responsible for learning and memory processes.

Pharmacological and Biochemical Characterization of TLQP-21 Activation of a Binding Site on CHO Cells.

VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF) has raised a huge interest and is one of most studied.

JMV5656, A Novel Derivative of TLQP-21, Triggers the Activation of a Calcium-Dependent Potassium Outward Current in Microglial Cells.

TLQP-21 (TLQPPASSRRRHFHHALPPAR) is a multifunctional peptide that is involved in the control of physiological functions, including feeding, reproduction, stress responsiveness, and general homeostasis. Despite the huge interest in TLQP-21 biological activity, very little is known about its intracellular mechanisms of action. In microglial cells, TLQP-21 stimulates increases of intracellular Ca that may activate functions, including proliferation, migration, phagocytosis and production of inflammatory molecules.

Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization.

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo.

The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis.

Insulin secretion control is critical for glucose homeostasis. Paracrine and autocrine molecules secreted by cells of the islet of Langerhans, as well as by intramural and autonomic neurons, control the release of different hormones that modulate insulin secretion. In pancreatic islets, the abundant presence of the granin protein VGF (nonacronymic; unrelated to VEGF) suggests that some of its proteolytically derived peptides could modulate hormone release.

The TLQP-21 peptide activates the G-protein-coupled receptor C3aR1 via a folding-upon-binding mechanism.

TLQP-21, a VGF-encoded peptide is emerging as a novel target for obesity-associated disorders. TLQP-21 is found in the sympathetic nerve terminals in the adipose tissue and targets the G-protein-coupled receptor complement-3a receptor1 (C3aR1). The mechanisms of TLQP-21-induced receptor activation remain unexplored.

In situ degradability and selected ruminal constituents of sheep fed with peanut forage hay.

Because legumes are a very important feed source for ruminants, the aim of this study was to evaluate the ideal inclusion level of hay Arachis pintoi cv. Belmonte in sheep diets by measuring the dry matter intake (DMI), concentration of volatile fatty acids, ammonia-nitrogen concentration, ruminal pH and the in situ degradability of dry matter (DM) and crude protein (CP). In the experiment with four sheep, a 4 × 4 Latin Square design was used with four periods and four treatments (0%, 30%, 60% and 100% Arachis replacing grass hay).

Biophysical characterization of a binding site for TLQP-21, a naturally occurring peptide which induces resistance to obesity.

Recently, we demonstrated that TLQP-21 triggers lipolysis and induces resistance to obesity by reducing fat accumulation [1]. TLQP-21 is a 21 amino acid peptide cleavage product of the neuroprotein VGF and was first identified in rat brain. Although TLQP-21 biological activity and its molecular signaling is under active investigation, a receptor for TLQP-21 has not yet been characterized.

Neuropeptide TLQP-21, a VGF internal fragment, modulates hormonal gene expression and secretion in GH3 cell line.

In the present study we demonstrated that TLQP-21, a biologically active peptide derived from the processing of the larger pro-VGF granin, plays a role in mammotrophic cell differentiation. We used an established in vitro model, the GH3 cell line, which upon treatment with epidermal growth factor develops a mammotrophic phenotype consisting of induction of prolactin expression and secretion, and inhibition of growth hormone. Here we determined for the first time that during mammotrophic differentiation, epidermal growth factor also induces Vgf gene expression and increases VGF protein precursor processing and peptide secretion.

TLQP-21, a VGF-derived peptide, stimulates exocrine pancreatic secretion in the rat.

The aims of this paper were to study: (1) the effects of TLQP-21 (non-acronic name), the C-terminal region of the VGF (non-acronic name), polypeptide (from residue 557 to 576 of VGF), on in vitro amylase release from rat isolated pancreatic lobules and acinar cells; (2) the mechanism through which TLQP-21 regulates exocrine pancreatic secretion, by using the muscarinic receptor antagonist atropine (10(-6)M) and the cyclo-oxygenase inhibitor, indomethacin (10(-6)M). On pancreatic lobules of rats, concentrations of TLQP-21 from 10(-7) to 10(-5)M significantly (p<0.05) induced a 2-3-fold increase of baseline pancreatic amylase release, measured at the end of 60 min incubation period.

Implication of the VGF-derived peptide TLQP-21 in mouse acute and chronic stress responses.

The impact of stress is widely recognized in the etiology of multiple disorders. In particular, psychological stress may increase the risk of cardiovascular, metabolic, immune, and mood disorders. Several genes are considered potential candidates to account for the deleterious consequences of stress and recent data point to role of Vgf.

Substance P activates ADAM9 mRNA expression and induces α-secretase-mediated amyloid precursor protein cleavage.

Altered levels of Substance P (SP), a neuropeptide endowed with neuroprotective and anti-apoptotic properties, were found in brain areas and spinal fluid of Alzheimer's disease (AD) patients. One of the hallmarks of AD is the abnormal extracellular deposition of neurotoxic beta amyloid (Aβ) peptides, derived from the proteolytic processing of amyloid precursor protein (APP). In the present study, we confirmed, the neurotrophic action of SP in cultured rat cerebellar granule cells (CGCs) and investigated its effects on APP metabolism.

Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21.

The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptor-mediated mechanism for any VGF peptide.

The extended granin family: structure, function, and biomedical implications.

The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers.

Characterization of the mechanisms involved in the gastric antisecretory effect of TLQP-21, a vgf-derived peptide, in rats.

TLQP-21, a vgf-derived peptide modulates gastric emptying and prevents ethanol-induced gastric lesions in rats. However, it remains to be studied whether or not TLQP-21 affects gastric acid secretion. In this study, we evaluated the effects of central (0.

Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding.

Although vgf gene knockout mice are hypermetabolic, administration of the VGF peptide TLQP-21 itself increased energy consumption. Agonist-antagonist roles are thus suggested for different VGF peptides, and the definition of their tissue heterogeneity is mandatory. We studied the rat stomach using antisera to C- or N-terminal sequences of known or predicted VGF peptides in immunohistochemistry and ELISA.

TLQP-21, a VGF-derived peptide, prevents ethanol-induced gastric lesions: insights into its mode of action.

Background And Aim: TLQP-21, a peptide derived from the vgf gene, has been reported to play a role in the regulation of rat gastric motility, but its influence on gastric mucosal integrity is unknown.

Experimental Approach: We investigated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric lesions in the rat.

Activation of kinase phosphorylation by heat-shift and mild heat-shock.

Most cells activate intracellular signalling to recover from heat damage. An increase of temperature, known as HS (heat shock), induces two major signalling events: the transcriptional induction of HSPs (heat-shock proteins) and the activation of the MAPK (mitogen-activated protein kinase) cascade. We performed the present study to examine the effects of HS, induced by different experimental conditions, on various kinases [ERK (extracellular-signal-regulated kinase), JNK (c-Jun N-terminal kinase), p38, Akt, AMPK (AMP-activated protein kinase) and PKC (protein kinase C)].